Investigation of HIV Incidence Rates in a High-Risk, High-Prevalence Kenyan Population: Potential Lessons for Intervention Trials and Programmatic Strategies.

Cost-effective HIV prevention programs should target persons at high risk of HIV acquisition. We conducted an observational HIV incidence cohort study in Kisumu, Kenya, where HIV prevalence is triple that of the national rate. We used referral and venue-sampling approaches to enroll HIV-negative persons for a 12-month observational cohort, August 2010 to September 2011, collected data using computer-assisted interviews, and performed HIV testing quarterly. Among 1292 eligible persons, 648 (50%) were excluded for HIV positivity and other reasons. Of the 644 enrollees, 52% were women who were significantly older than men (P<.01). In all, 7 persons seroconverted (incidence rate [IR] per 100 person-years=1.11; 95% confidence interval [CI] 0.45-2.30), 6 were women; 5 (IR=3.14; 95% CI 1.02-7.34) of whom were ≤25 years. Most new infections occurred in young women, an observation consistent with other findings in sub-Saharan Africa that women aged ≤25 years are an important population for HIV intervention trials in Africa.

Measles outbreak in a highly vaccinated population, San Diego, 2008: role of the intentionally undervaccinated.

OBJECTIVE: In January 2008, an intentionally unvaccinated 7-year-old boy who was unknowingly infected with measles returned from Switzerland, resulting in the largest outbreak in San Diego, California, since 1991. We investigated the outbreak with the objective of understanding the effect of intentional undervaccination on measles transmission and its potential threat to measles elimination. METHODS: We mapped vaccination-refusal rates according to school and school district, analyzed measles-transmission patterns, used discussion groups and network surveys to examine beliefs of parents who decline vaccination, and evaluated containment costs. RESULTS: The importation resulted in 839 exposed persons, 11 additional cases (all in unvaccinated children), and the hospitalization of an infant too young to be vaccinated. Two-dose vaccination coverage of 95%, absence of vaccine failure, and a vigorous outbreak response halted spread beyond the third generation, at a net public-sector cost of $10 376 per case. Although 75% of the cases were of persons who were intentionally unvaccinated, 48 children too young to be vaccinated were quarantined, at an average family cost of $775 per child. Substantial rates of intentional undervaccination occurred in public charter and private schools, as well as public schools in upper-socioeconomic areas. Vaccine refusal clustered geographically and the overall rate seemed to be rising. In discussion groups and survey responses, the majority of parents who declined vaccination for their children were concerned with vaccine adverse events. CONCLUSIONS: Despite high community vaccination coverage, measles outbreaks can occur among clusters of intentionally undervaccinated children, at major cost to public health agencies, medical systems, and families. Rising rates of intentional undervaccination can undermine measles elimination.

Mumps resurgences in the United States: A historical perspective on unexpected elements.

In 2006 the United States experienced the largest nationwide mumps epidemic in 20 years, primarily affecting college dormitory residents. Unexpected elements of the outbreak included very abrupt time course (75% of cases occurred within 90 days), geographic focality (85% of cases occurred in eight rural Midwestern states), rapid upward and downward shift in peak age-specific attack rate (5-9-year olds to 18-24-year olds, then back), and two-dose vaccine failure (63% of case-patients had received two doses). To construct a historical context in which to understand the recent outbreak, we reviewed US mumps surveillance data, vaccination coverage estimates, and relevant peer-reviewed literature for the period 1917-2008. Many of the unexpected features of the 2006 mumps outbreak had been reported several times previously in the US, e.g., the 1986-1987 mumps resurgence had extremely abrupt onset, rural geographic focality, and an upward-then-downward age shift. Evidence suggested recurrent mumps outbreak patterns were attributable to accumulation of susceptibles in dispersed situations where the risk of endemic disease exposure was low and were triggered when this susceptible population was brought together in crowded living conditions. The 2006 epidemic followed this pattern, with two unique variations: it was preceded by a period of very high vaccination rates and very low disease incidence and was characterized by two-dose failure rates among adults vaccinated in childhood. Data from the past 80 years suggest that preventing future mumps epidemics will depend on innovative measures to detect and eliminate build-up of susceptibles among highly vaccinated populations.

Persistence of rubella antibodies after 2 doses of measles-mumps-rubella vaccine.

BACKGROUND: Since 1990, most schoolchildren in the United States have received a second dose of measles-mumps-rubella vaccine (MMR2) at kindergarten entry. Elimination of endemic rubella virus circulation in the United States was declared in 2004. The objective of the current study was to evaluate the short- and long-term rubella immunogenicity of MMR2. METHODS: At enrollment in 1994-1995, children (n = 307) in a rural Wisconsin health maintenance organization received MMR2 at age 4-6 years. A comparison group of older children (n = 306) was vaccinated at age 9-11 years. Serum specimens were collected during a 12-year period. Rubella antibody levels were evaluated by plaque-reduction neutralization (lowest detectable titer, 1:10). RESULTS: Before administration of MMR2 in the kindergarten group, 9% of subjects were seronegative, 60% had the lowest detectable titer, and the geometric mean titer (GMT) was 1:13. One month after administration of MMR2, 1% were seronegative, 6% had the lowest detectable titer, and the GMT was 1:42. Four-fold boosts occurred in 62% of subjects, but only 0.3% were immunoglobulin M positive. Twelve years after MMR2 administration, 10% were seronegative, 43% had the lowest detectable titer, and the GMT was 1:17. The middle-school group showed similar patterns. CONCLUSIONS: Rubella antibody response to MMR2 was vigorous, but titers decreased to pre-MMR2 levels after 12 years. Because rubella is a highly epidemic disease, vigilance will be required to assure continued elimination.

Persistence of mumps antibodies after 2 doses of measles-mumps-rubella vaccine.

BACKGROUND: Since 1990, most US schoolchildren have received a second dose of measles-mumps-rubella vaccine (MMR2) at kindergarten entry. The objective of the present study was to evaluate the short- and long-term mumps immunogenicity of MMR2. METHODS: At enrollment in 1994-1995, children (n=308) in a rural Wisconsin health maintenance organization received MMR2 at age 4-6 years. A comparison group of older children (n=308) was vaccinated at age 9-11 years. Serum samples were collected over 12 years. Mumps antibody levels were evaluated by plaque-reduction neutralization (lowest detectable titer, 10). RESULTS: Before MMR2, the geometric mean titer (GMT) for the younger group was 33; no subject was seronegative, but 16% had the lowest detectable titer. In response to MMR2, the GMT tripled to 97, and the proportion with low titers diminished to 3%. Four-fold boosts occurred among 54%, but only 3% were positive for immunoglobulin M. Twelve years after MMR2, the GMT declined to 46, the proportion with titers

Mumps vaccination coverage and vaccine effectiveness in a large outbreak among college students--Iowa, 2006.

Following implementation of a routine childhood two-dose measles-mumps-rubella vaccination strategy, mumps disease levels dropped dramatically in the US and an elimination goal was set for 2010. However, a 2006 epidemic involved >5700 cases nationwide, with many reported among fully vaccinated college students. In an outbreak in two Iowa colleges, we investigated: (1) vaccination coverage using electronic records verified by provider records and (2) vaccine effectiveness assessed by comparison of dose-specific attack rates. Mumps was classified as typical (parotitis/orchitis) or atypical (parotid tenderness or submandibular/sublingual adenitis). Two-dose mumps vaccination coverage was 90% both for the student population (2128/2363) and case-students (97/108). Two-dose vaccine effectiveness was 76-88% with no significant difference for attack rates between one and two doses. Among two-dose vaccine recipients, 74% of the population (1482/2009) and 79% of the case-students (75/95) had received the second dose >10 years before. A large mumps outbreak occurred despite high two-dose vaccination coverage in a population most of whom had received the second dose >10 years before. Two-dose vaccine effectiveness was similar to previous one-dose estimates. Further studies are needed to examine the persistence of two-dose mumps vaccine-induced immunity and to determine whether US mumps elimination can be achieved with the current vaccination strategy.

Persistence of measles antibodies after 2 doses of measles vaccine in a postelimination environment.

OBJECTIVE: To evaluate the persistence of measles antibodies after 2 doses of measles vaccine in a setting where exposure to wild-type measles was unlikely. Measles was declared eliminated from the United States in 2000, an achievement attributed to effective implementation of a routine 2-dose vaccination policy. Some have questioned whether measles transmission could resume if immunity wanes in the absence of boosting from wild-type measles. DESIGN: Prospective, observational, volunteer cohort study. SETTING: Rural Wisconsin health maintenance organization. PARTICIPANTS: Children who received the second measles vaccine dose at kindergarten (aged 4-6 years) or middle school (aged 10-12 years) in 1994 or 1995. Serum samples were collected periodically during a 10-year period for the kindergarten group and a 5-year period for the middle school group. INTERVENTION: Second dose of measles vaccine. MAIN OUTCOME MEASURE: Measles antibody levels were assessed by plaque-reduction neutralization: titers less than 8 mIU/mL were considered seronegative and suggestive of susceptibility to measles, and titers of 120 mIU/mL or less were considered low and suggestive of potential susceptibility. RESULTS: During the study period, no measles was reported in the study area. Voluntary attrition reduced the study population from 621 at enrollment to 364 (58.6%) by study end. Before the second dose, 3.1% (19/621) had low titers, of whom 74% (14/19) were antibody-negative, with geometric mean titers being significantly higher in kindergarteners (1559 mIU/mL) than in middle schoolers (757 mIU/mL) and rates of negativity significantly lower (1.0% [3/312] vs 3.6% [11/309]). One month after the second dose, 0.2% (1/612) had low titers and none was seronegative, with geometric mean titers being significantly higher in kindergarteners (2814 mIU/mL) than in middle schoolers (1672 mIU/mL). By study end, 4.9% (18/364) had low titers and none was seronegative, with no significant difference in geometric mean titers between kindergarteners (641 mIU/mL) and middle schoolers (737 mIU/mL) when both groups were aged 15 years. Projections suggest that the proportion of persons with low antibody levels may increase over time. CONCLUSIONS: Measles antibody persisted in all vaccinees available for follow-up 10 years after a second dose of vaccine, with no seronegative results detected. Declining titers suggest the need for vigilance in ensuring disease protection for the vaccinated population.

Evaluation of potentially common adverse events associated with the first and second doses of measles-mumps-rubella vaccine.

BACKGROUND/OBJECTIVES: In 1989, the American Academy of Pediatrics and the Advisory Committee on Immunization Practices recommended that school children receive 2 doses of measles-mumps-rubella vaccine. With measles and rubella eliminated from the United States, measles-mumps-rubella vaccine adverse events have come under scrutiny, but no study has compared the reactogenicity of the first (measles-mumps-rubella vaccine dose 1) and second (measles-mumps-rubella vaccine dose 2) doses at the most common ages of administration in the United States. METHODS: From a health maintenance organization, 3 groups of children were recruited: (1) toddlers aged 12 to 24 months receiving measles-mumps-rubella vaccine dose 1; (2) kindergartners aged 4 to 6 years receiving measles-mumps-rubella vaccine dose 2; and (3) middle schoolers aged 10 to 12 years receiving measles-mumps-rubella vaccine dose 2. From 2 weeks before measles-mumps-rubella vaccine administration until 4 weeks afterward, families recorded in diaries the occurrence of potentially common symptoms. Postvaccination symptom rates were compared with the prevaccination baseline, with significance assessed by testing incidence rate ratios estimated by Poisson regression. RESULTS: Of 2173 children enrolled, 373 (17%) were lost to attrition, producing a study population of 1800. Compared with the prevaccination baseline, rates of fever, diarrhea, and rash were significantly elevated postvaccination among 535 toddlers receiving measles-mumps-rubella vaccine dose 1. An estimated net 95 (18%) experienced measles-mumps-rubella vaccine-associated events (median onset 5-10 days postvaccination, duration 2-5 days), with high fever (temperature > or = 39.5 degrees C) occurring in 33 (6%). None required medical attention. For 633 kindergartners and 632 middle schoolers, symptom rates were not significantly elevated after measles-mumps-rubella vaccine dose 2 compared with baseline. CONCLUSIONS: Vaccination-associated adverse events occur in approximately 1 of every 6 toddlers receiving measles-mumps-rubella vaccine dose 1, with high fever occurring in 1 of 20. Adverse events are infrequent for measles-mumps-rubella vaccine dose 2 administered to school-aged children.

Implications of a 2005 measles outbreak in Indiana for sustained elimination of measles in the United States.

BACKGROUND: Measles was declared eliminated from the United States in 2000 but remains endemic worldwide. In 2005, a 17-year-old unvaccinated girl who was incubating measles returned from Romania, creating the largest documented outbreak of measles in the United States since 1996. METHODS: We conducted a case-series investigation, molecular typing of viral isolates, surveys of rates of vaccination coverage, interviews regarding attitudes toward vaccination, and cost surveys. RESULTS: Approximately 500 persons attended a gathering with the index patient one day after her return home. Approximately 50 lacked evidence of measles immunity, of whom 16 (32 percent) acquired measles at the gathering. During the six weeks after the gathering, a total of 34 cases of measles were confirmed. Of the patients with confirmed measles, 94 percent were unvaccinated, 88 percent were less than 20 years of age, and 9 percent were hospitalized. Of the 28 patients who were 5 to 19 years of age, 71 percent were home-schooled. Vaccine failure occurred in two persons. The virus strain was genotype D4, which is endemic in Romania. Although containment measures began after 20 persons were already infectious, measles remained confined mostly to children whose parents had refused to have them vaccinated, primarily out of concern for adverse events from the vaccine. Seventy-one percent of patients were from four households. Levels of measles-vaccination coverage in Indiana were 92 percent for preschoolers and 98 percent for sixth graders. Estimated costs of containing the disease were at least 167,685 dollars, including 113,647 dollars at a hospital with an infected employee. CONCLUSIONS: This outbreak was caused by the importation of measles into a population of children whose parents had refused to have them vaccinated because of safety concerns about the vaccine. High vaccination levels in the surrounding community and low rates of vaccine failure averted an epidemic. Maintenance of high rates of vaccination coverage, including improved strategies of communication with persons who refuse vaccination, is necessary to prevent future outbreaks and sustain the elimination of measles in the United States.

Individually significant risk factors do not provide an accurate clinical prediction rule for infant underimmunization in one disadvantaged urban area.

OBJECTIVE: To define a clinical prediction rule for underimmunization in children of low socioeconomic status. METHODS: We assessed a cohort of 1160 infants born from July 1998 through June 1999 at an urban safety net hospital that received primary care at 4 community health centers. The main outcome measure was up-to-date status with the 3:2:2:2 infant vaccine series at 12 months of age. RESULTS: Latino infants (n = 959, 83% of cohort) had immunization rates of 74%, at least 18% higher than any other racial/ethnic group. Multivariate logistic regression demonstrated the following independent associations (relative risk, 95% confidence interval) for inadequate immunization: non-Latino ethnicity (1.7, 1.4-2.0), maternal smoking (1.3, 1.1-1.7), no health insurance (1.9, 1.4-2.3), late prenatal care (1.9, 1.5-2.3), no pediatric chronic condition (2.1, 1.2-3.1), and no intent to breast-feed (1.3, 1.1-1.6). However, the index of concordance (c-index) for this model was only 0.69. Neither excluding infants who left the health care system nor accounting for infants who were "late starters" for their first vaccines improved the predictive accuracy of the model. CONCLUSIONS: In this predominantly Latino population of low socioeconomic status, Latino infants have higher immunization rates than other infants. However, we were unable to develop a model to reliably predict which infants in this population were underimmunized. Models to predict underimmunization should be tested in other settings. In this population, interventions to improve immunization rates must be targeted at all children without respect to individual risk factors.

Measles transmission and vaccine effectiveness during a large outbreak on a densely populated island: implications for vaccination policy.

BACKGROUND: The Republic of the Marshall Islands (RMI) is a South Pacific nation freely associated with the United States. In 2003, the RMI experienced the largest measles outbreak within the United States or its associated areas for more than a decade, although the reported coverage of 1-dose measles-mumps-rubella (MMR) vaccine was 80%-93%. The outbreak ended only after vaccination of >35,000 persons among a population of 51,000. Of outbreak cases, 41% were reported to have been previously vaccinated. We studied measles attack rates in RMI households to assess vaccine effectiveness and patterns of disease transmission. METHODS: For the household secondary attack rate study, households were selected by convenience sampling of outbreak measles cases. The primary case was defined as the first person with measles in a household. Secondary cases were household members with measles onset 7-18 days after the primary case's rash onset. Vaccine effectiveness analysis was limited to children aged 6 months to 14 years, with vaccination status verified against written records. RESULTS: Seventy-two households were included in the study. The median household size was 11 persons, and the median number of persons per room was 5.5. Secondary cases were more likely than primary cases to be infants (46% vs. 13%; P=.03). MMR vaccine effectiveness was 92% (95% confidence interval [CI], 67%-98%) for 1 dose and 95% (95% CI, 82%-98%) for 2 doses. CONCLUSIONS: Measles vaccine effectiveness was high; thus, diminished effectiveness was not the main cause of the outbreak. In communities with high population density and household crowding, very high population immunity is needed to prevent measles outbreaks and to protect infants below the age of vaccination. This may require excellent implementation of a routine 2-dose measles vaccination strategy.

The cost of containing one case of measles: the economic impact on the public health infrastructure--Iowa, 2004.

BACKGROUND: In February 2004, students from a college in Iowa, with a high proportion of nonmedical exemptions to vaccination, traveled to India; one fourth of the students contracted measles while there. One exposed, susceptible student returned home during his infectious period, necessitating 2 months of containment efforts in Iowa. OBJECTIVE: The objective of this study was to measure the direct costs of measles containment from a public health system perspective. METHODS: We evaluated activities performed, personnel time/materials allocated, and direct costs incurred in 2004 US dollars by the Iowa public health infrastructure. The study period was defined as March 5, 2004 (when the Iowa Department of Public Health was first contacted about the case), through May 12, 2004 (when a final meeting was held on the containment effort). RESULTS: A total of 2525 hours of personnel time were expended to review flight manifests, contact exposed passengers, set up vaccination clinics, trace >1000 potentially exposed contacts, and institute and enforce quarantine orders for vaccination refusers. Two thousand twenty-five phone calls were received from the public, and 2243 miles were driven by staff. The temporal distribution of personnel time was characterized by marked peaks at the report of potential secondary cases. The total estimated cost was 142452 dollars. CONCLUSIONS: The direct cost to the public health infrastructure of containing 1 case of measles was far greater than the estimated cost of uncomplicated individual illness (less than 100 dollars). Economic analyses of vaccine-preventable diseases may need to go beyond the costs of individual illness to account for the costs of protecting society.

Pertussis in adolescents and adults: should we vaccinate?

BACKGROUND: The incidence of reported pertussis among adolescents, adults, and young infants has increased sharply over the past decade. Combined acellular pertussis vaccines for adolescents and adults are available in Canada, Australia, and Germany and may soon be considered for use in the United States. OBJECTIVE: To evaluate the potential health benefits, risks, and costs of a national pertussis vaccination program for adolescents and/or adults. DESIGN, SETTING, AND POPULATION: The projected health states and immunity levels associated with pertussis disease and vaccination were simulated with a Markov model. The following strategies were examined from the health care payer and societal perspectives: (1) no vaccination; (2) 1-time adolescent vaccination; (3) 1-time adult vaccination; (4) adult vaccination with boosters; (5) adolescent and adult vaccination with boosters; and (6) postpartum vaccination. Data on disease incidence, costs, outcomes, vaccine efficacy, and adverse events were based on published studies, recent unpublished clinical trials, and expert panel input. MAIN OUTCOME MEASURES: Cases prevented, adverse events, costs (in 2004 US dollars), cost per case prevented, and cost per quality-adjusted life-year (QALY) saved. RESULTS: One-time adolescent vaccination would prevent 30800 cases of pertussis (36% of projected cases) and would result in 91000 vaccine adverse events (67% local reactions). If pertussis vaccination cost $15 and vaccine coverage was 76%, then 1-time adolescent vaccination would cost $1100 per case prevented (or $1200 per case prevented) or $20000 per QALY (or $23000 per QALY) saved, from the societal (or health care payer) perspective. With a threshold of $50000 per QALY saved, the adolescent and adult vaccination with boosters strategy became potentially cost-effective from the societal perspective only if 2 conditions were met simultaneously, ie, (1) the disease incidence for adolescents and adults was > or =6 times higher than base-case assumptions and (2) the cost of vaccination was less than $10. Adult vaccination strategies were more costly and less effective than adolescent vaccination strategies. The results were sensitive to assumptions about disease incidence, vaccine efficacy, frequency of vaccine adverse events, and vaccine costs. CONCLUSIONS: Routine pertussis vaccination of adolescents results in net health benefits and may be relatively cost-effective.

Health-state valuations for pertussis: methods for valuing short-term health states.

BACKGROUND: The incidence of reported adolescent and adult pertussis continues to rise in the United States. Acellular pertussis vaccines for adolescents and adults have been developed and may be available soon for use in the U.S. Our objectives were: (1) to describe patient valuations of pertussis disease and vaccination; and (2) to compare valuations for short-term and long-term health states associated with pertussis. METHODS: We conducted telephone surveys with 515 adult patients and parents of adolescent patients with pertussis in Massachusetts to determine valuations of pertussis-related health states for disease and vaccination using time trade-off (TTO) and contingent valuation (CV) techniques. Respondents were randomized to complete either a short-term or long-term TTO exercise. Discrimination between health states for each valuation technique was assessed using Tukey's method, and valuations for short-term vs. long-term health states were compared using the Wilcoxon rank-sum test. RESULTS: Three hundred three (59%) and 309 (60%) respondents completed and understood the TTO and CV exercises, respectively. Overall, respondents gave lower valuations (lower TTO and higher CV values) to avoid a given state for adolescent/adult disease compared to vaccine adverse events. Infant complications due to pertussis were considered worse than adolescent/adult disease, regardless of the method of valuation. The short-term TTO resulted in lower mean valuations and larger mean differences between health states than the long-term TTO exercise. CONCLUSION: Pertussis was considered worse than adverse events due to vaccination. Short-term health-state valuation is better able to discriminate among health states, which is useful for cost-utility analysis.

Ensuring preparedness for potential poliomyelitis outbreaks: Recommendations for the US poliovirus vaccine stockpile from the National Vaccine Advisory Committee (NVAC) and the Advisory Committee on Immunization Practices (ACIP).

Paralytic poliomyelitis was once endemic in the United States; however, because of high vaccination levels, the last case of wild disease occurred in 1979. Although worldwide polio eradication may be achieved in the near future, the presence of undervaccinated children in urban areas and among groups who refuse vaccination creates an outbreak risk, should importation of wild virus occur. In 1999, the Advisory Committee on Immunization Practices (ACIP) recommended that inactivated poliovirus vaccine (IPV) be used for routine immunization of the US population and that oral poliovirus vaccine (OPV) be reserved for "mass vaccination campaigns to control outbreaks of paralytic polio." Subsequently, the sole US manufacturer of OPV withdrew from the market. In 2003, a joint National Vaccine Advisory Committee (NVAC)/ACIP working group was charged with reporting to its parent bodies concerning the need for a poliovirus vaccine stockpile. Based on that working group's report, the NVAC and ACIP have concluded that stockpiles of both IPV and OPV should be maintained. In the event of an outbreak in which OPV continues not to be available, IPV should be used for control, and a stockpile of 8 million doses seems to be sufficient. Should IPV be manufactured only in combination with other vaccines, appropriate procurement actions should be taken to ensure that uncombined IPV continues to be stockpiled. Under circumstances of diminished population immunity, OPV may offer outbreak control advantages. The NVAC and ACIP recommend that the United States collaborate with international agencies to provide guaranteed and rapid access to at least 8 million doses of trivalent OPV or 8 million doses of each of the 3 types of monovalent OPV. The regulatory and practical obstacles to implementation of this recommendation will require assertive facilitation at high levels of the federal government and careful planning at the state and local levels.

Societal costs and morbidity of pertussis in adolescents and adults.

BACKGROUND: Since the 1980s, the reported incidence of pertussis among adolescents and adults has been steadily increasing. To understand whether the benefits of an acellular pertussis vaccine formulated for adolescents and adults might offset its costs, policy makers will need information about morbidity and societal (medical and nonmedical) costs of pertussis. METHODS: Adolescents (age, 10-17 years) and adults (age, >or=18 years) with confirmed pertussis illness were identified by the Massachusetts enhanced pertussis surveillance system. We evaluated medical costs in a cohort of patients who had confirmed pertussis during the period of January 1998 through December 2000; nonmedical costs, by means of prospective interviews, in a cohort of patients who had confirmed pertussis during the period of December 2001 through January 2003; and morbidity in both cohorts. Our main outcome measures were mean costs per case, in 2002 US dollars. RESULTS: In the analysis of medical costs, 1679 adolescents and 936 adults were found to have mean costs of 242 dollars and 326 dollars, respectively (P<.05). In interviews with 314 adolescents and 203 adults, adults had significantly higher nonmedical costs (447 dollars) than those of adolescents (155 dollars). A total of 83% of adolescents missed a mean of 5.5 days from school (range, 0.4-32 days), and 61% of adults missed a mean of 9.8 days from work (range, 0.1-180 days) because of pertussis. Thirty-eight percent of adolescents and 61% of adults were still coughing at the time of the interview, which occurred an average of 106 days and 94 days, respectively, after cough onset. CONCLUSIONS: Pertussis causes significant morbidity in and costs for adolescents and adults, with time losses comprising the largest proportion of the cost. Societal costs should be considered when making decisions about potential vaccine use in the future.

The impact of reminder-recall interventions on low vaccination coverage in an inner-city population.

BACKGROUND: Reminder-recall interventions have improved immunization rates in numerous studies. OBJECTIVE: To evaluate the impact of large-scale, registry-based reminder-recall interventions on low immunization rates in an inner-city population. DESIGN: Randomized, controlled, effectiveness trial. SETTING: Fulton County, Georgia. PARTICIPANTS: A total of 3050 children (76% black, 14% Hispanic, 7% white, and 3% other or unknown; median age, 9 months; range, 1-14 months) identified in an immunization registry as receiving health care in the public sector. INTERVENTIONS: Each child was randomly assigned to 1 of 4 groups: control (usual care), autodialer (automated telephone or mail reminder recall), outreach (in-person telephone, mail, or home visit recall), and combination (autodialer with outreach backup). Interventions continued until the child reached 24 months of age. MAIN OUTCOME MEASURE: Completion by the age of 24 months of the 4-3-1-3 vaccination series based on intention-to-treat analysis. RESULTS: A total of 260 (34%) of the 763 patients in the control group, 306 (40%) of the 763 in the autodialer group, 284 (37%) of the 760 in the outreach group, and 293 (38%) of 764 in the combination group completed the vaccination series. CONCLUSION: Large-scale, registry-based reminder-recall interventions produced only small improvements in low immunization rates of an inner-city population.

Strategies to improve immunization rates and well-child care in a disadvantaged population: a cluster randomized controlled trial.

OBJECTIVE: To measure the effect of a multimodal intervention on well-child care visit (WCV) and immunization rates in an inner-city population. DESIGN: Cluster randomized controlled trial. SETTING AND PARTICIPANTS: One-year cohort of 2843 infants born at a hospital in an integrated inner-city health care system. INTERVENTIONS: Eleven clinics were randomly allocated to 1 of 3 study arms: WCV intervention (n = 3), immunization intervention (n = 4), and controls (n = 4). Interventions to improve immunization and WCV rates included both patient-based and clinic-based activities. MAIN OUTCOME MEASURES: Up-to-date status with childhood immunizations and WCVs by age 12 months (primary) and health care utilization and charges (secondary). RESULTS: Compared with the control arm, the WCV and immunization arms had 5% to 6% higher immunization rates and 7% to 8% higher WCV rates. In multivariate analyses that accounted for the clustered nature of the data, the number of immunizations received was greater in the WCV arm than in controls. However, neither the WCV nor the immunization intervention increased WCV or immunization up-to-date rates. The WCV arm had slightly higher health care charges. Neither intervention affected emergency, urgent care or inpatient utilization. CONCLUSIONS: This multimodal intervention produced a small increase in the number of childhood immunizations delivered. However, patient- and clinic-based methods did not lead to significant increases in WCV or immunization up-to-date rates after controlling for other factors. Methods found in some settings to increase immunization up-to-date rates may not be as effective in a population of inner-city socioeconomically disadvantaged children.

Primary-care visits and hospitalizations for ambulatory-care-sensitive conditions in an inner-city health care system.

OBJECTIVE: Hospitalizations for ambulatory-care-sensitive conditions (ACSCs) are a marker for access barriers for children and a possible outcome measure for primary-care interventions. We assessed the relationship between primary-care utilization and subsequent ACSC hospitalization among inner-city children. METHODOLOGY: We conducted a nested, case-control study of children born in 1993 in Denver Health (DH), a "safety-net" delivery system in Denver, Colo. Utilization of preventive care and other primary-care services was compared between children hospitalized for ACSCs and nonhospitalized children, who were matched by age and duration of care. Comparisons were adjusted for demographics, payer, and chronic health conditions. RESULTS: Of 2531 children, 115 (4.5%) were hospitalized for ACSCs. Sixty-eight percent were Hispanic, and 78% were enrolled in Medicaid. Children with ACSC hospitalization and nonhospitalized children made a similar number of preventive-care visits (2.7 +/- 2.0 vs 3.0 +/- 2.1 visits, P =.30) and other primary-care visits (4.4 +/- 4.6 vs 3.6 +/- 4.6, P =.16) between birth and hospitalization (for cases) or the same time period (for controls). After multivariate adjustment, each additional preventive-care visit (odds ratio = 0.87; 95% confidence interval: 0.67-1.12) was associated with a nonsignificant reduction in the risk of hospitalization for ACSC. CONCLUSIONS: Because ACSC hospitalizations are uncommon and the association between primary care and subsequent hospitalization is weak, a reduction in ACSC hospitalizations may not be a feasible outcome measure for interventions to increase the rate of preventive- or primary-care visits for underserved children within individual delivery systems.

Immunization registry accuracy: improvement with progressive clinical application.

BACKGROUND: Healthcare systems have been challenged to ensure the timely administration of immunizations. Immunization registries have been proposed to improve the accuracy and completeness of immunization information and to promote effective practice. METHODS: Comparison of randomly selected samples from two birth cohorts (1993 and 1998) from Denver Health Medical Center. Chart review and immunization registry information for these groups were compared; a composite immunization was recorded and up-to-date (UTD) status established. Registry data were compared with this composite using a sensitivity measure to assess completeness and accuracy. RESULTS: Among 818 children in the 1993 cohort and 1043 children in the 1998 cohort, there were 6386 and 6886 valid immunizations, respectively. The registry recorded 71.4% and 97.7% of these for the 1993 and 1998 cohorts, respectively (p <0.001). The apparent UTD rate, as measured with registry data alone, improved from 37% to 79% between the two time frames (p <0.001). Composite UTD status was 83.1% and 78.9% (1993 vs 1998, respectively). Accurate registry-defined UTD status improved from 44.4% to 100% between the two intervals. CONCLUSIONS: Immunization registry accuracy improved dramatically for recorded immunizations and UTD status. However, after 3 years of registry use, the overall proportion of children who were UTD had not significantly improved. The mere presence of a registry does not ensure more complete vaccination coverage. Other registry-based strategies, including use of the data for reminder, recall, and audit, may further improve immunization coverage.